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- Gao, TL, et al.
(författare)
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Antinociceptive Effects of Sinomenine Combined With Ligustrazine or Paracetamol in Animal Models of Incisional and Inflammatory Pain
- 2021
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Ingår i: Frontiers in physiology. - : Frontiers Media SA. - 1664-042X. ; 11, s. 523769-
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Tidskriftsartikel (refereegranskat)abstract
- The management of postoperative and inflammatory pain has been a pressing challenge in clinical settings. Sinomenine (SN) is a morphinan derived alkaloid with remarkable analgesic properties in various kinds of pain models. The aim of the current study is to investigate if SN can enhance the effect of ligustrazine hydrochloride (LGZ) or paracetamol (PCM) in animal models of postoperative and inflammatory pain. And to determine if the combined therapeutic efficacies can be explained by pharmacokinetics changes. Pharmacological studies were performed using a rat model of incisional pain, and a mouse model of carrageenan induced inflammatory pain. Pharmacokinetic studies were performed using a microdialysis sampling and HPLC-MS/MS assay method to quantify SN, LGZ, and PCM levels in blood and extracellular fluid in brain. We found that SN plus LGZ or SN plus PCM produced marked synergistic analgesic effects. However, such synergy was subjected to pain modalities, and differed among pain models. Pharmacological discoveries could be partially linked to pharmacokinetic alterations in SN combinations. Though further evaluation is needed, our findings advocate the potential benefits of SN plus LGZ for postoperative pain management, and SN plus PCM for controlling inflammatory pain.
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| 6. |
- Gao, X, et al.
(författare)
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Longitudinal patient-reported outcomes 1 year after thoracoscopic segmentectomy versus lobectomy for early-stage lung cancer: a multicentre, prospective cohort study protocol
- 2023
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Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 13:1, s. e067841-
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Tidskriftsartikel (refereegranskat)abstract
- Segmentectomy and lobectomy are the main surgical procedures for early-stage lung cancer. However, few studies have analysed patient-reported outcomes after segmentectomy versus lobectomy. This study aims to compare patient-reported outcomes—such as symptoms, daily functioning and quality of life—between thoracoscopic segmentectomy and lobectomy for early-stage lung cancer during the 1 year after surgery.Methods and analysisOverall, 788 newly diagnosed patients with early-stage lung cancer (tumour size ≤2 cm), who are scheduled to undergo thoracoscopic segmentectomy or lobectomy, will be recruited in this multicentre, prospective cohort study. The patients will receive standardised care after surgery. The Perioperative Symptom Assessment for Lung Surgery—a validated lung cancer surgery-specific scale—will be used to assess the symptoms and functions at baseline, at discharge and monthly after discharge for 1 year. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 and Lung Cancer module 29 will be used to assess the patients’ quality of life at the same time points. The primary outcome will be the shortness of breath scores during the first year after thoracoscopic segmentectomy and lobectomy and will be compared using mixed-effects models. The secondary outcomes will include other symptoms, indicators of daily functioning, quality of life scores and traditional clinical outcomes. These will be compared using mixed-effects models and the Student’s t-test, non-parametric test or Χ2test. Propensity score matching will be used to ensure an even distribution of known confounders between the groups.Ethics and disseminationThe Ethics Committee for Medical Research and New Medical Technology of Sichuan Cancer Hospital approved this study (approval number: SCCHEC-02-2022-002). All participants will be instructed to provide informed consent. The manuscript is based on protocol version 3.0. The study results will be presented at medical conferences and published in peer-reviewed journals.Trial registration numberChiCTR2200060753.
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- Mishra, A, et al.
(författare)
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Diminishing benefits of urban living for children and adolescents' growth and development
- 2023
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 615:7954, s. 874-883
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Tidskriftsartikel (refereegranskat)abstract
- Optimal growth and development in childhood and adolescence is crucial for lifelong health and well-being1–6. Here we used data from 2,325 population-based studies, with measurements of height and weight from 71 million participants, to report the height and body-mass index (BMI) of children and adolescents aged 5–19 years on the basis of rural and urban place of residence in 200 countries and territories from 1990 to 2020. In 1990, children and adolescents residing in cities were taller than their rural counterparts in all but a few high-income countries. By 2020, the urban height advantage became smaller in most countries, and in many high-income western countries it reversed into a small urban-based disadvantage. The exception was for boys in most countries in sub-Saharan Africa and in some countries in Oceania, south Asia and the region of central Asia, Middle East and north Africa. In these countries, successive cohorts of boys from rural places either did not gain height or possibly became shorter, and hence fell further behind their urban peers. The difference between the age-standardized mean BMI of children in urban and rural areas was <1.1 kg m–2 in the vast majority of countries. Within this small range, BMI increased slightly more in cities than in rural areas, except in south Asia, sub-Saharan Africa and some countries in central and eastern Europe. Our results show that in much of the world, the growth and developmental advantages of living in cities have diminished in the twenty-first century, whereas in much of sub-Saharan Africa they have amplified.
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- Chen, XD, et al.
(författare)
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Non-invasive early detection of cancer four years before conventional diagnosis using a blood test
- 2020
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1, s. 3475-
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Tidskriftsartikel (refereegranskat)abstract
- Early detection has the potential to reduce cancer mortality, but an effective screening test must demonstrate asymptomatic cancer detection years before conventional diagnosis in a longitudinal study. In the Taizhou Longitudinal Study (TZL), 123,115 healthy subjects provided plasma samples for long-term storage and were then monitored for cancer occurrence. Here we report the preliminary results of PanSeer, a noninvasive blood test based on circulating tumor DNA methylation, on TZL plasma samples from 605 asymptomatic individuals, 191 of whom were later diagnosed with stomach, esophageal, colorectal, lung or liver cancer within four years of blood draw. We also assay plasma samples from an additional 223 cancer patients, plus 200 primary tumor and normal tissues. We show that PanSeer detects five common types of cancer in 88% (95% CI: 80–93%) of post-diagnosis patients with a specificity of 96% (95% CI: 93–98%), We also demonstrate that PanSeer detects cancer in 95% (95% CI: 89–98%) of asymptomatic individuals who were later diagnosed, though future longitudinal studies are required to confirm this result. These results demonstrate that cancer can be non-invasively detected up to four years before current standard of care.
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- Gao, J, et al.
(författare)
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The unsynchronized changes of CT image and nucleic acid detection in COVID-19: reports the two cases from Gansu, China
- 2020
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Ingår i: Respiratory research. - : Springer Science and Business Media LLC. - 1465-993X. ; 21:1, s. 96-
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- The novel coronavirus disease (COVID-19) outbreak started in December 2019 in Wuhan, China, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The CT image is used to assess the disease progress, whereas the continued two times of negative results from SARS-CoV-2 nucleic acid detection had been considered as a criterion for ending antiviral treatment. We compared the two COVID-19 cases with similar backgrounds and CT image repeated intervals under treatment. Our report highlighted the unsynchronized expression in the changes of CT image and nucleic acid detection in COVID-19, and lasting positive nucleic acid test result in patients recovered from pneumonia. It may be contributed to recognize the disease and improve prevention.
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| 20. |
- Gao, SN, et al.
(författare)
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Identification of a prognostic risk-scoring model and risk signatures based on glycosylation-associated cluster in breast cancer
- 2022
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Ingår i: Frontiers in genetics. - : Frontiers Media SA. - 1664-8021. ; 13, s. 960567-
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Tidskriftsartikel (refereegranskat)abstract
- Breast cancer is a heterogeneous disease whose subtypes represent different histological origins, prognoses, and therapeutic sensitivity. But there remains a strong need for more specific biomarkers and broader alternatives for personalized treatment. Our study classified breast cancer samples from The Cancer Genome Atlas (TCGA) into three groups based on glycosylation-associated genes and then identified differentially expressed genes under different glycosylation patterns to construct a prognostic model. The final prognostic model containing 23 key molecules achieved exciting performance both in the TCGA training set and testing set GSE42568 and GSE58812. The risk score also showed a significant difference in predicting overall clinical survival and immune infiltration analysis. This work helped us to understand the heterogeneity of breast cancer from another perspective and indicated that the identification of risk scores based on glycosylation patterns has potential clinical implications and immune-related value for breast cancer.
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| 28. |
- Pelaz, B, et al.
(författare)
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Diverse Applications of Nanomedicine
- 2017
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Ingår i: ACS nano. - : American Chemical Society (ACS). - 1936-086X .- 1936-0851. ; 11:3, s. 2313-2381
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Tidskriftsartikel (refereegranskat)
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| 33. |
- Wang, XJ, et al.
(författare)
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Identification of a Potentially Functional microRNA-mRNA Regulatory Network in Lung Adenocarcinoma Using a Bioinformatics Analysis
- 2021
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Ingår i: Frontiers in cell and developmental biology. - : Frontiers Media SA. - 2296-634X. ; 9, s. 641840-
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Tidskriftsartikel (refereegranskat)abstract
- Lung adenocarcinoma (LUAD) is a common lung cancer with a high mortality, for which microRNAs (miRNAs) play a vital role in its regulation. Multiple messenger RNAs (mRNAs) may be regulated by miRNAs, involved in LUAD tumorigenesis and progression. However, the miRNA–mRNA regulatory network involved in LUAD has not been fully elucidated.MethodsDifferentially expressed miRNAs and mRNA were derived from the Cancer Genome Atlas (TCGA) dataset in tissue samples and from our microarray data in plasma (GSE151963). Then, common differentially expressed (Co-DE) miRNAs were obtained through intersected analyses between the above two datasets. An overlap was applied to confirm the Co-DEmRNAs identified both in targeted mRNAs and DEmRNAs in TCGA. A miRNA–mRNA regulatory network was constructed using Cytoscape. The top five miRNA were identified as hub miRNA by degrees in the network. The functions and signaling pathways associated with the hub miRNA-targeted genes were revealed through Gene Ontology (GO) analysis and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. The key mRNAs in the protein–protein interaction (PPI) network were identified using the STRING database and CytoHubba. Survival analyses were performed using Gene Expression Profiling Interactive Analysis (GEPIA).ResultsThe miRNA–mRNA regulatory network consists of 19 Co-DEmiRNAs and 760 Co-DEmRNAs. The five miRNAs (miR-539-5p, miR-656-3p, miR-2110, let-7b-5p, and miR-92b-3p) in the network were identified as hub miRNAs by degrees (>100). The 677 Co-DEmRNAs were targeted mRNAs from the five hub miRNAs, showing the roles in the functional analyses of the GO analysis and KEGG pathways (inclusion criteria: 836 and 48, respectively). The PPI network and Cytoscape analyses revealed that the top ten key mRNAs were NOTCH1, MMP2, IGF1, KDR, SPP1, FLT1, HGF, TEK, ANGPT1, and PDGFB. SPP1 and HGF emerged as hub genes through survival analysis. A high SPP1 expression indicated a poor survival, whereas HGF positively associated with survival outcomes in LUAD.ConclusionThis study investigated a miRNA–mRNA regulatory network associated with LUAD, exploring the hub miRNAs and potential functions of mRNA in the network. These findings contribute to identify new prognostic markers and therapeutic targets for LUAD patients in clinical settings.
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| 34. |
- Wang, XJ, et al.
(författare)
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Multi-Omics Integration-Based Prioritisation of Competing Endogenous RNA Regulation Networks in Small Cell Lung Cancer: Molecular Characteristics and Drug Candidates
- 2022
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Ingår i: Frontiers in oncology. - : Frontiers Media SA. - 2234-943X. ; 12, s. 904865-
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Tidskriftsartikel (refereegranskat)abstract
- The competing endogenous RNA (ceRNA) network-mediated regulatory mechanisms in small cell lung cancer (SCLC) remain largely unknown. This study aimed to integrate multi-omics profiles, including the transcriptome, regulome, genome and pharmacogenome profiles, to elucidate prioritised ceRNA characteristics, pathways and drug candidates in SCLC.MethodWe determined the plasma messenger RNA (mRNA), microRNA (miRNA), long noncoding RNA (lncRNA) and circular RNA (circRNA) expression levels using whole-transcriptome sequencing technology in our SCLC plasma cohort. Significantly expressed plasma mRNAs were then overlapped with the Gene Expression Omnibus (GEO) tissue mRNA data (GSE 40275, SCLC tissue cohort). Next, we applied a multistep multi-omics (transcriptome, regulome, genome and pharmacogenome) integration analysis to first construct the network and then to identify the lncRNA/circRNA-miRNA-mRNA ceRNA characteristics, genomic alterations, pathways and drug candidates in SCLC.ResultsThe multi-omics integration-based prioritisation of SCLC ceRNA regulatory networks consisted of downregulated mRNAs (CSF3R/GAA), lncRNAs (AC005005.4-201/DLX6-AS1-201/NEAT1-203) and circRNAs (hsa_HLA-B_1/hsa_VEGFC_8) as well as upregulated miRNAs (hsa-miR-4525/hsa-miR-6747-3p). lncRNAs (lncRNA-AC005005.4-201 and NEAT1-203) and circRNAs (circRNA-hsa_HLA-B_1 and hsa_VEGFC_8) may regulate the inhibited effects of hsa-miR-6747-3p for CSF3R expression in SCLC, while lncRNA-DLX6-AS1-201 or circRNA-hsa_HLA-B_1 may neutralise the negative regulation of hsa-miR-4525 for GAA in SCLC. CSF3R and GAA were present in the genomic alteration, and further identified as targets of FavId and Trastuzumab deruxtecan, respectively. In the SCLC-associated pathway analysis, CSF3R was involved in the autophagy pathways, while GAA was involved in the glucose metabolism pathways.ConclusionsWe identified potential lncRNA/cirRNA-miRNA-mRNA ceRNA regulatory mechanisms, pathways and promising drug candidates in SCLC, providing novel potential diagnostics and therapeutic targets in SCLC.
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| 35. |
- Wu, ZC, et al.
(författare)
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Tumor suppressor ZHX2 inhibits NAFLD-HCC progression via blocking LPL-mediated lipid uptake
- 2020
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Ingår i: Cell death and differentiation. - : Springer Science and Business Media LLC. - 1476-5403 .- 1350-9047. ; 27:5, s. 1693-1708
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Tidskriftsartikel (refereegranskat)abstract
- Non-alcoholic fatty liver disease (NAFLD) leads to hepatocellular carcinoma (HCC). However, the underlying mechanism remains largely unclear. Here, we investigated the role of the tumor suppressor Zinc fingers and homeoboxes 2 (ZHX2) in the progression of NAFLD to HCC. ZHX2 expression was significantly decreased in fatty liver tissues, especially in the liver with NAFLD–HCC. ZHX2 overexpression disturbed lipid homeostasis of cultured HCC cells, and inhibited lipid deposition in hepatocytes both in vitro and in vivo. Moreover, ZHX2 inhibited uptake of exogenous lipids through transcriptional suppression of lipid lipase (LPL), leading to retarded proliferation of HCC cells. Importantly, LPL overexpression significantly reversed ZHX2-mediated inhibition of HCC cell proliferation, xenograft tumor growth, lipid deposition, and spontaneous liver tumor formation. Consistently, IHC staining demonstrated a negative correlation of ZHX2 with LPL in an HCC cohort. Collectively, ZHX2 protects hepatocytes from abnormal lipid deposition in NAFLD through transcriptional repression of LPL, which subsequently retards cell growth and NAFLD–HCC progression. These findings illustrate a novel mechanism of NAFLD progression into HCC.
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- Zhang, QY, et al.
(författare)
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Autocrine Activity of Extracellular Vesicles Induced by Icariin and Its Effectiveness in Glucocorticoid-Induced Injury of Bone Microvascular Endothelial Cells
- 2022
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Ingår i: Cells. - : MDPI AG. - 2073-4409. ; 11:12
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Tidskriftsartikel (refereegranskat)abstract
- Glucocorticoids could induce injury and apoptosis of bone microvascular endothelial cells (BMECs) in the femoral head, which is associated with the development of osteonecrosis and osteoporosis. Icariin is a prenylated flavonol glycoside isolated from Epimedium brevicornum, serving as the main active pharmaceutical constituent to treat bone loss. Currently, the impact of the autocrine activity of extracellular vesicles (EVs) induced by icariin on the glucocorticoid-induced injury of BMECs is still to be confirmed. In this study, EVs were isolated from BMECs treated with and without icariin by super-speed centrifugation. Although icariin treatment would not significantly change the size and total protein content of BMECs-derived EVs, expression of EVs-carried vascular endothelial growth factor (VEGF) and transforming growth factor β1 (TGF-β1) was enhanced and numerous miRNAs involved in cell proliferation and apoptosis were upregulated (e.g., hsa-miR-1469 and hsa-miR-133a-5p) or downregulated (e.g., hsa-miR-10b-5p) (p < 0.05). A total of 29 differentially expressed inflammatory factors were detected between the EVs secreted by BMECs from the Icariin-treated group and the Model group. The EVs secreted by BMECs could improve cell viability, decrease cell apoptosis, and promote cell migration and angiogenesis under the intervention of glucocorticoids. Meanwhile, icariin intervention could reinforce these protective effects of BMECs-derived EVs. To sum up, the present study indicates that icariin acts as a promising candidate for treating glucocorticoid-induced injury of BMECs and bone diseases, partially through the autocrine activity of EVs. In vivo or animal studies are still required to better understand the function of BMECs-derived EVs.
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